Combination of Decitabine and Temozolomide in the Treatment of Patients With Metastatic Melanoma

NCT00715793 | Completed Phase 1 Results DMC

• 1 other identifier: UPCI 07-008
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

The combination of TMZ and DAC may effect dual modulation of DNA repair genes resulting in improved clinical response.

Conditions

Malignant Melanoma

Keywords

Decitabine; Temozolomide; Metastatic; Melanoma; Non-resectable; Stage IIIB melanoma; stage IV melanoma; TMZ; DTIC; promoter methylation; skin cancer; chemotherapy

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants That Experienced a Dose Limiting Toxicity (DLT)

  Dose-limiting toxicities (DLTs) were defined as grade 4 neutropenia or thrombocytopenia which lasts \>7 days; grade 3 or 4 febrile neutropenia; grade 3 or greater non-hematological toxic effects.

  Up to 26 months

• Overall Response Rate (ORR)

  Using RECIST v1.0 criteria, overall response rate (ORR) was determined by the number of participants with complete response (CR) + the number of participants with partial response (PR) / the number of participants with complete response (CR) + the number of participants with partial response (PR) + the number of participants with stable disease (SD) + the number of participants with progressive disease (PD), multiplied by 100. Per RECIST v1.0 criteria (assessed by MRI or CT): Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response (PR) nor sufficient increase to to qualify for Progressive Disease (PD); PD, 20% increase in the sum if target lesion or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions.

  Up to 30 months

• Recommended Phase 2 Dose (RP2D) of DAC + TMZ

  Toxicity assessments used CTCAE v3.0. Two dose levels were explored in the phase I portion of the study. A modified 3 + 3 'up and down' design was used. Given the knowledge that DAC exhibits its epigenetic effects at 30-fold lower doses than at its maximum-tolerated dose (MTD), escalation of DAC to the MTD was not done.

  Up to 26 months

Secondary Outcomes (5)

• Disease Control Rate (DCR)

  Up to 30 months

• Progression-free Survival (PFS)

  Up to 42 months

• 6-month Progression-free Survival (PFS) Rate

  6 months

• Overall Survival (OS)

  Up to 42 months

• 1-year Overall Survival (OS) Rate

  12 months

Study Arms (1)

Single Arm

EXPERIMENTAL

Drug: Decitabine; Drug: Temozolomide; Procedure: biopsy

Interventions

Decitabine DRUG

In Part I patients will be treated on a standard "3+3" phase I dose-escalation design starting at 0.075 mg/kg until a decitabine dose level of 0.15 mg/kg is reached, or, in case unacceptable toxicities are observed, at the maximum tolerated dose (Phase II recommended dose). Decitabine will be administered at the specified dose level, intravenously, daily 5 days a week for the first 2 weeks of a 6-week cycle.

Also known as: DTIC

Single Arm

Temozolomide DRUG

Temozolomide is available in 25 mg and 100 mg tablets that will be administered orally; doses will be rounded to the nearest 25 mg. Temozolomide will be administered orally at 75 mg/m2 daily for 4 weeks starting on week 2 of a 6-week cycle.

Also known as: TMZ

Single Arm

biopsy PROCEDURE

Fine needle aspirates (FNA) and/or core biopsies of tumor samples will be obtained from consenting patients with accessible, evaluable disease, on days 1, 8, 15, and 29 of the first cycle and when patients go off study. Biopsies are optional in Phase I and required for all consenting subjects in Phase II.

Also known as: fine needle aspirate, FNA, core biopsy

Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who have non-resectable Stage IIIB or stage IV metastatic melanoma that have progressed despite prior therapies.
• Life expectancy of at least 12 weeks.
• ECOG performance status of 0, 1 and 2.
• ≥18 years of age.
• Patients who have not received any other chemotherapeutic, biological or investigational agent within 28 days of study drug administration.
• First line and active brain metastases (metastatic lesions to the brain that have been adequately treated with surgery and/or appropriate radiation therapy and that have documented stability for \>4 weeks or \>2 weeks if treated with stereotactic radiosurgery, remain eligible)

You may not qualify if:

• Any evidence of renal dysfunction (proteinuria, estimated creatinine clearance from serum creatinine test of \<60 ml/min).
• Impaired hepatic function (liver enzymes greater than twice the upper limit of normal or bilirubin \> 2.0 except in patients with Gilbert's syndrome).
• Prior treatment with alkylating agents (including TMZ and DTIC).
• Active brain metastases (metastatic lesions to the brain that have been adequately treated with surgery and/or appropriate radiation therapy and that have documented stability for \>4 weeks remain eligible).
• Active infections or serious general medical conditions.
• Female patients of child-bearing age who are not on adequate contraception, or are pregnant or breast-feeding.

Sponsors & Collaborators

• Hussein Tawbi: lead
• Eisai Inc.: collaborator
• Schering-Plough: collaborator

Study Sites (1)

UPMC Cancer Centers

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Melanoma; Neoplasm Metastasis; Skin Neoplasms

Interventions

Decitabine; Dacarbazine; Temozolomide; Biopsy; Biopsy, Needle

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Triazenes; Imidazoles; Azoles; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Punctures

Results Point of Contact

• Title: Hussein Tawbi, MD, PhD
• Organization: University of Pittsburgh

HTawbi@mdanderson.org

713-792-6111

Study Officials

• Hussein Tawbi, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 27, 2008
• First Posted: July 15, 2008
• Study Start: June 1, 2008
• Primary Completion: May 1, 2015
• Study Completion: August 1, 2015
• Last Updated: October 3, 2017
• Results First Posted: October 3, 2017

Record last verified: 2017-09

Locations

US (1)